Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo-and Hypoglycemia

Abstract

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and pre-vents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated coun-terregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are un-clear. In this study, 11 subjects without diabetes with severe obesity were investigated pre-and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by18 F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post-versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normogly-cemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post-and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hy-poglycemia, attenuated responses of counterregula-tory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post-versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be fur-ther elucidated.